Guillain-Barré syndrome following the 2009 pandemic monovalent and seasonal trivalent influenza vaccination campaigns in Spain from 2009 to 2011: outcomes from active surveillance by a neurologist network, and records from a country-wide hospital discharge database

Abstract

Background: Studies have shown a slight excess risk in Guillain-Barré syndrome (GBS) incidence associated with A(H1N1)pdm09 vaccination campaign and seasonal trivalent influenza vaccine immunisations in 2009-2010. We aimed to assess the incidence of GBS as a potential adverse effect of A(H1N1)pdm09 vaccination.

Methods: A neurologist-led network, active at the neurology departments of ten general hospitals serving an adult population of 4.68 million, conducted GBS surveillance in Spain in 2009-2011. The network, established in 1996, carried out a retrospective and a prospective study to estimate monthly alarm thresholds in GBS incidence and tested them in 1998-1999 in a pilot study. Such incidence thresholds additionally to observation of GBS cases with immunisation antecedent in the 42 days prior to clinical onset were taken as alarm signals for 2009-2011, since November 2009 onwards. For purpose of surveillance, in 2009 we updated both the available centres and the populations served by the network. We also did a retrospective countrywide review of hospital-discharged patients having ICD-9-CM code 357.0 (acute infective polyneuritis) as their principal diagnosis from January 2009 to December 2011.

Results: Among 141 confirmed of 148 notified cases of GBS or Miller-Fisher syndrome, Brighton 1-2 criteria in 96 %, not a single patient was identified with clinical onset during the 42-day time interval following A(H1N1)pdm09 vaccination. In contrast, seven cases were seen during a similar period after seasonal campaigns. Monthly incidence figures did not, however, exceed the upper 95 % CI limit of expected incidence. A retrospective countrywide review of the registry of hospital-discharged patients having ICD-9-CM code 357.0 (acute infective polyneuritis) as their principal diagnosis did not suggest higher admission rates in critical months across the period December 2009-February 2010.

Conclusions: Despite limited power and underlying reporting bias in 2010-2011, an increase in GBS incidence over background GBS, associated with A(H1N1)pdm09 monovalent or trivalent influenza immunisations, appears unlikely.

Keywords: Guillain-Barré syndrome; ICD-9-CM; Influenza A virus H1N1 subtype; Influenza vaccines; Public health surveillance; Safety.

Fig. 1

Geographical distribution of cities where study hospitals provided neurological care for Guillain-Barré syndrome. The inset shows Canary Islands. This figure is slightly modified from Cuadrado et al. [22]. Copyright 2004, with permission of Springer

Fig. 2

Seasonal patterns of Guillain-Barré syndrome (GBS) according to the neurologist network. Top: monthly incidence of GBS in two age groups. Bottom: case distribution by type of preceding infection and month of clinical onset

Fig. 3

Predicted Guillain-Barré syndrome (GBS) background incidence with its 95 % confidence limits; monthly incidence of GBS among the population under surveillance as observed by the neurologist network during the period 2009–2010, seasonal and A(H1N1)pdm09 influenza vaccination campaigns (in the latter case with monthly number of doses for the whole population from 16 November 2009 to 1 February 2010, and routine campaign intervals —marked between vertical green lines—for seasonal immunisations), clinical antecedents (black arrows) and clinical onset of GBS patients (red arrows) immunised during the 42-day prior to clinical onset; and monthly incidence of GBS during the surveillance period, as seen from country-wide diagnostic data on 2383 hospital-admitted patients over 20 years and having GBS coded as ICD-9-CM 357.0 as their principal diagnosis at discharge (Discharge Certificates, National In-Patient Hospital Registry)